Epidemiologic profile of inflammatory bowel disease in Eastern Mediterranean Region (EMRO) countries: a systematic review and meta-analysis

Background Inflammatory bowel disease (IBD) consists of two main types: Crohn’s disease (CD) and ulcerative colitis (UC). The epidemiology of IBD patients has not been comprehensively studied in EMRO countries; therefore, we conducted this meta-analysis to study the epidemiology of this disease in these countries. Methods We searched four international databases, namely Scopus, Web of Knowledge (ISI), Medline/PubMed, and ProQuest, from inception up to the end of May 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline was used to carry out this systematic review and meta-analysis investigation. Using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist, the quality of the selected papers was assessed. Results Based on the results of this study, the incidence of UC in EMRO countries was 2.65 per 100,000 (95% CI: 1.39–3.90), and the incidence of CD was 1.16 per 100,000 (95% CI: 0.73–1.59). The most commonly involved intestinal segment in CD was the terminal ileum (44.7%, 95% CI: 34.7–55.2), followed by the ileum (29.8%, 95% CI: 22.2–38.6), and colon (18.7%, 95% CI: 10.8–30.4). However, in UC patients, extensive colitis was the most common finding (32.3%, 95% CI: 26.4–38.8), followed by proctosigmoiditis (27.9%, 95% CI: 21.1–35.8), left-sided colitis (27.4%, 95% CI: 22.7–32.7), and proctitis (22.6%, 95% CI: 17.5–28.5). Conclusion As a result, we were able to establish the traits of IBD patients in EMRO nations. UC patients had a higher incidence than CD patients. The most common regions of involvement in CD and UC patients, respectively, were the colon and pancolitis. Compared to UC patients, CD patients had a higher history of appendectomy. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-024-18816-z.


Introduction
Inflammatory bowel disease (IBD) has two main subtypes contains ulcerative colitis (UC) and Crohn's disease (CD).This disease is becoming a global concern with increasing prevalence and incidence worldwide [1].Like other Gastrointestinal diseases, IBD has imposed considerable burden globally along with significant population suffering from this condition [2,3].Almost 6.8 million cases of IBD were recognized in 2017 globally with the prevalence rate and death rate of 84.3 and 0.51 respectively [4].It is estimated 2.5 million people in US and 1 million people in Europe suffering from IBD [2].According to Global Burden of Disease (GBD) statements, North America and Caribbean were the countries with the highest and lowest prevalence of IBD respectively [4].A study in the UK revealed that the prevalence of IBD has raised 33.8% between 2006 and 2016 [5].A time-trend analysis has shown that 75% of CD surveys and 60% of UC studies demonstrated a statistically significant growing incidence [6].In addition, in a study conducted by Caviglia et al., the incidence of IBD was increased from 200 per 100,000 in 2006 to 321.2 per 100,000 in 2021 presenting an increased rate of 46 percent [7].
IBD may occur as a result of the uncontrolled immune system response, which can originate from genetic or environmental determinants [8].Environmental factors and hereditary susceptibility are the most important cause of the IBD and its course.These two factors arouse the immune system to act over active and impaired [9,10].Smoking, low physical activity, hygiene status, surgeries, and antibiotic consumption are some environmental factors associated with IBD [11].Based on the epidemiological models, environmental factors can affect individuals based on a person's genetic characteristics, including age, gender, personality, and physical state, causing IBD susceptibility [10,12].Eastern Mediterranean Regional Office (EMRO) includes 22 countries which is one of the World Health Organization regional classifications [13].The epidemiology of IBD was studies in the EMRO countries separately but a comprehensive study to assess IBD epidemiology was lacking hence we performed a comprehensive metaanalysis study to investigated epidemiological status of IBD in this region.

Setting
The goal of the present research project is to determine the epidemiology of IBD in the EMRO nations by a systematic review and meta-analysis.The Systematic Review and Meta-analysis (PRISMA) protocol was used for executing the study [14].

Search strategy
We searched four international databases, namely Scopus, Web of Knowledge (ISI), Medline/PubMed, and Pro-Quest, from inception up to the end of May 2023.The search strategy and keywords are presented in Table 1.

Inclusion and exclusion criteria
Case-control, cross-sectional, and cohort studies assessing IBD, CD, or UC individuals in the EMRO countries' population with the following criteria were eligible to be included in our study: IBD diagnosis confirmed by clinical characteristics of the individuals and endoscopy or colonoscopy confirmation.At least one of the following outcomes reported: The smoking rate in patients, family history, sites of involvement, risk factors of patients, incidence rate.Studies in English.Available full text.Studies which didn't fulfill the inclusion criteria were excluded.Two researchers independently selected the studies, and any disagreements were resolved by the third researcher.

Quality assessment
Using The Joanna Briggs Institute (JBI) Critical Appraisal Checklist, two independent researchers conducted the quality assessment of included cross-sectional, case-control, and cohort articles.Any disagreements were finalized by face-to-face consultation and the contribution of a third researcher.The JBI checklist scores of included studies are shown in Table 2.

Data extraction
Included papers were carefully studied by two researchers.The following outcomes were extracted: Name of the first author, year of publication, region of study, duration of study, sample size of study, mean age of participants.The features of included studies are shown in Table 2.

Statistical analysis
Version 2 of the statistical software for comprehensive meta-analysis (CMA) was employed for this investigation.When three trials were available for a particular outcome, the data were pooled.To ascertain the amount of result heterogeneity, Cochran's test (where the significance level was deemed less than 0.1) and I2 statistics (where the significant level was deemed greater than 50%) were obtained.When heterogeneity was significant, the random-effects model was utilized; otherwise, the fixed-effects model was used.

Results
A total of 1671 studies were found in the initial search.After omitting the duplications, 1485 studies underwent screening.Two researchers independently screened the title, abstract, and, when necessary, the full text of the articles.A total of 1416 articles were deleted, and 69 papers underwent full-text revision.Finally, 34 studies that met our inclusion criteria were selected for our study (Fig. 1).

Description of studies
The basic characteristics of the included studies are presented in Table 2 .Based on the geographical location of the 34 included studies, 14 studies were conducted in Iran, 9 in Saudi Arabia, 3 in Kuwait, 1 in Qatar, 1 in Bahrain, 1 in the UAE, 1 in Lebanon, 1 in Oman, 1 in Pakistan, 1 in Tunisia, and 1 in Egypt.The summary characteristics of the studies are shown in Table 2.

Incidence of IBD patients
According to the results of the meta-analysis, the incidence of UC in EMRO countries was 2.6 per 100,000 (95% CI: 1.3-3.9),and the incidence of CD was 1.16 per 100,000 (95% CI: 0.7-1.5)(Fig. 2A and B).

Prevalence of IBD among men and women
Based on our meta-analysis, 46% of Ulcerative Colitis diagnoses in EMRO are from men.However, this number is 55% for Crohn Disease (Fig. 2C and D).

Age at diagnosis
The mean age at diagnosis for Ulcerative Colitis is 32.7 (95% CI: 30.3 to 35.1).In addition, the mean age at diagnosis is 30.9 (95% CI: 27.1 to 34.7) for Crohn Disease (Fig. 2E and F).

Result of heterogeneity assessment
As we used random effect model for our main analyses, we presented the detailed information about possible heterogeneity for each outcome in the Table 3.We also evaluated the distribution of true effect using prediction interval (See supplementary material).

Discussion
In this study we surveyed the epidemiology of IBD in the EMRO countries.We assessed the incidence of IBD, sites of involvement in GI tract and risk factors.
According to the findings of our study, the incidence rates for UC and CD in the EMRO region were 2.65 and 1.16, respectively.Different nations have distinct rates of incidence and prevalence for IBD and its subtypes.The highest frequency of IBD was found in Europe and North America, according to a comprehensive review and meta-analysis by Ng et al.The incidence of IBD in North America and Europe appeared to be steady or declining based on the findings of this study [1].The annual incidence rate of CD was reported to be 0.5 per 100,000 in Japan and 20.2 per 100,000 in Canada.In Japan, there were 5.8 UC patients per 100,000 people, compared to 319 UC patients per 100,000 people in Canada [49,50].The incidence and prevalence of UC were reported to be 0.3 and 7.6 per 100,000 people in South Korea, respectively [51].In the United States, prior research places the incidence of UC and CD, respectively, at 10.1 to 12 and 6.3 to 7.9 per 100,000 people [52].By comparing the findings of our study with those of other studies, we have come to the conclusion that the incidence of UC and CD is higher in the EMRO region than in eastern nations like Japan and South Korea, and lower than in eastern nations.We believe this variation is caused by varying genetic vulnerability, environmental circumstances, and lifestyle choices.
With regard to the findings of our study, CD patients had slightly higher incident rate of smoking (12.2%) than UC patients (11%).In a cohort study conducted by Lunney et al., CD patients had a greater prevalence of smoking than UC patients [53].Smoking is a difficult component in IBD.Even though it increases the risk of CD, patients with UC benefited from it [54][55][56].Smoking's impact on IBD patients was shown to follow a dosage response pattern [45].Smoking's effects on IBD patients can be influenced by genetic and ethnic factors [57,58].
Positive family history is one of the major risk factors for IBD patients [59].A person's genetic and environmental susceptibilities that they inherited from their parents are reflected in their positive family history in IBD patients [60].First degree relatives and monozygotic twins have a higher incidence of IBD, which supports the hereditary component to IBD [61].In this study, we demonstrated that UC (11.7%) and CD (11.3%) have slightly higher positive family history rates.Family members of UC patients were much more numerous than CD patients in a meta-analysis research by Childres et al. [62].Asian, African American, Hispanic, and White populations all had higher rates of positive family history, ranging from 26 to 33%, 9% to 18%, 9% to 16%, and 5.9%, respectively [63][64][65][66][67].
Based to the results obtained in our study, CD patients were more likely to undergo an appendectomy (15.5%) than UC patients (4.8%).Appendectomy's impact on the course of IBD is debatable.According to research by Andersson et al., appendectomy for inflammatory diseases such appendicitis reduces the incidence of UC [68].Higher risk of CD and UC after appendectomy was found in a different cohort research by Chung et al. [69].Five years after surgery, an appendectomy significantly reduced the risk of UC in another trial [70].
CD can affect any part of the gastrointestinal tract in a discontinuous manner, whereas UC is limited to the rectum and colon [71].In this study, we observed that the most common pattern of GI tract involvement in UC patients is extensive colitis (32.3%), followed by proctosigmoiditis (27.9%).For CD patients, the most frequent pattern of involvement was coloileal, followed by the ileum.Previous studies have reported that proctitis and proctosigmoiditis occur in 46% of UC patients, while leftsided colitis and extensive colitis affect 17% and 37% of UC individuals, respectively [72].

Limitation
Our research had some limitations.First, some of the EMRO region's nations lacked the appropriate literature for our analysis.Second, we do not have adequate data to conduct subgroup analyses based on gender, age, and marital status.Third, we do not have enough

Conclusions
In conclusion, our study identified the characteristics of patients with inflammatory bowel disease (IBD) in EMRO countries.We observed a higher incidence of ulcerative colitis (UC) compared to Crohn's disease (CD) patients.Coloileal involvement was the most common site of disease in CD patients, whereas extensive colitis was the predominant pattern in UC patients.Additionally, a history of appendectomy was more frequent among CD patients than UC patients.

Fig. 2 A
Fig. 2 A Incidence of UC in EMRO countries, B Incidence of UC in EMRO countries, C Prevalence of Ulcerative Colitis among men, D Prevalence of Crohn Disease among men, E Mean Age at diagnosis for Ulcerative Colitis, F Mean Age at diagnosis for Crohn Disease, G Terminal ileum involvement in CD, H Ileal involvement in CD, I Colon involvement in CD

Fig. 3 A
Fig. 3 A Extensive colitis involvement in UC, B Proctosigmoiditis involvement in UC, C Left sided colitis involvement in UC patients, D Proctitis involvement in UC, E Prevalence of smoking in CD patients, F Prevalence of smoking in UC patients, G Prevalence of positive family history in UC patients, H Prevalence of positive family history in CD patients, I (Upper figure): History of appendectomy in CD patients, J (Lower figure): History of appendectomy in UC patients

Table 2
Basic characteristics of included studies

name Country Study period Study design Population Gender Sample size Mean age Mean age at diagnosis Level of quality Male Female UC CD IBD UC CD IBD UC CD IBD Al
Awar, 2004 [15]

Table 3
The results of heterogeneity